HECW1

protein-coding

HECT, C2 and WW domain containing E3 ubiquitin protein ligase 1, the group of HECT domain containing|MicroRNA protein coding host genes|C2 domain containing

Gene summary

Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in regulation of dendrite morphogenesis and ubiquitin-dependent protein catabolic process. Located in cytosol. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_015052.5

Inheritance

—

ClinVar variants

U:209B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.16

Max pathogenic AF

—

Genomic locus

chr7:43,112,629-43,566,001

External References & Databases

Ensembl (ENSG00000002746)

Transcript & Mutation Effects

hg38 • Region Span ~453.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HECW1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 200

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015052.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	1 clinvar	2 clinvar	4
missense			201 clinvar	2 clinvar		203
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	209	3	2	214

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 26 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015052.5	RefSeq	NP_055867.3	28	MANE Select
ENST00000395891.7	Ensembl	ENSP00000379228.1	28	MANE Select
NM_001287059.2	RefSeq	NP_001273988.1	27	Standard
ENST00000429529.1	Ensembl	ENSP00000413336.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signaling by WNT
Signal Transduction
Degradation of DVL
TCF dependent signaling in response to WNT

Biological Process

protein polyubiquitination
ubiquitin-dependent protein catabolic process
protein ubiquitination
proteasome-mediated ubiquitin-dependent protein catabolic process
positive regulation of protein catabolic process

Molecular Function

ubiquitin protein ligase activity

Cellular Component

cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000395891
Coding exons: 28
Length: 453403
Individuals with no LoFs: 124795
Homozygous LoFs: 0
Heterozygous LoFs: 21
Defined: 124816
p: 0.0000841

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.95	733	995	0.737	0.0000641	10499
Missense (PolyPhen)		236	399.09	0.59134		4128
Synonymous	1.17	392	422	0.928	0.0000310	3140
Loss of Function	7.22	14	86.4	0.162	0.00000522	886

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00018	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000056	0.000056	rare
Finnish	0.000093	0.000093	rare
European (Non-Finnish)	0.000098	0.000097	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent degradation of DVL1. Also targets the mutant SOD1 protein involved in familial amyotrophic lateral sclerosis (FALS). Forms cytotoxic aggregates with DVL1, SSR3 and mutant SOD1 that lead to motor neuron death in FALS. {ECO:0000269|PubMed:14684739}.;

Recessive Scores

pRec: 0.174

Intolerance Scores

RVIS EVS: -0.43
RVIS percentile EVS: 24.72

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.643

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium